Many of the specialized properties of endothelial cells are a function of specific receptors and enzymes that are present on their surface. Activation of endothelial cells by a variety of stimuli causes striking changes in their expression of cell surface molecules and in their functional properties. Glycosphingolipids (GSLs) are cell surface molecules that are receptors and immunogens. A number of blood group and tumor-associated antigens are glycolipids, and autoantibodies to several glycolipids have been identified recently. Although endothelial cells have been the subject of intensive biochemical investigation, prior to our work no information was available about the GSLs of these cells. We have recently identified the major neutral GSLs and gangliosides of human umbilical vein endothelial cells. The long term objectives of our work are to determine whether an immunological attack on endothelial cell GSLs plays a role in the pathogenesis of vascular damage, and whether these GSLs are cell surface receptors for regulatory molecules or cells. The specific aims of this proposal are to identify changes in the composition and cell surface expression of GSLs of lymphokine-activated endothelial cells; to determine if cell surface GSLs mediate binding of cells or adhesion proteins to activated endothelial cells; and to analyze human sera for the presence of autoantibodies against endothelial cell GSL antigens. These studies will provide new information about an important class of endothelial cell surface molecules, and will evaluate the role of GSLs as receptors for immune cells and autoantibodies as a cause of vascular damage and atherosclerosis.